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Background: In temporal lobe epilepsy (TLE), estimating the potential risk of language dysfunction before surgery is a necessary procedure. Functional MRI (fMRI) is considered the most useful to determine language lateralization noninvasively. However, there are no standardized language fMRI protocols, and several issues remain unresolved. In particular, the language tasks normally used are predominantly active paradigms that require the overt participation of patients, making assessment difficult for pediatric patients or patients with intellectual disabilities. In this study, task-based fMRI with passive narrative listening was applied to evaluate speech comprehension to estimate language function in Japanese-speaking patients with drug-resistant TLE. Methods: Twenty-one patients (six with intellectual disabilities) participated. Patients listened to passive auditory stimuli with combinations of forward and silent playback, and forward and backward playback. The activation results were extracted using a block design, and lateralization indices were calculated. The obtained fMRI results were compared to the results of the Wada test. Results: The concordance rate between fMRI and the Wada test was 95.2%. Meaningful responses were successfully obtained even from participants with intellectual disabilities. Conclusions: This passive fMRI paradigm can provide safe and easy presurgical language evaluation, particularly for individuals who may not readily engage in active paradigms. [ABSTRACT FROM AUTHOR]

Background: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10–30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA). Methods: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial. Results: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance. Conclusions: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects. [ABSTRACT FROM AUTHOR]

Giant serpentine aneurysms are rare huge and partially thrombosed aneurysms, with an eccentric tortuous intra-aneurysmal vascular channel. Surgical treatment is often necessary due to the great mass effect. We describe a case of a left-handed woman with a giant serpentine aneurysm of the left middle cerebral artery whose management was complex. The challenge was to exclude the aneurysm from circulation, reduce the mass effect, and, mostly, preserve the language function. Since the patient was left-handed the language dominance needed to be assessed; functional MRI (fMRI) and Wada test (WT) showed a right dominance. Surgical treatment was performed, as a complication, the patient developed left fronto-basal ischemia with a slight paresis of the right hand but without any language deficit. Our case shows the importance of a multidisciplinary team in patient management, with a pivotal role of neuroradiological functional tests in presurgical planning.

Background: For patients with drug-resistant epilepsy, surgery may be effective in controlling their disease. Surgical evaluation may involve localization of the language areas using functional magnetic resonance imaging (fMRI) or Wada testing. We evaluated the accuracy of task-based fMRI versus Wada-based language lateralization in a cohort of our epilepsy patients. Methods: In a single-center, retrospective analysis, we identified patients with medically intractable epilepsy who participated in presurgical language mapping (n = 35) with fMRI and Wada testing. Demographic variables and imaging metrics were obtained. We calculated the laterality index (LI) from task-evoked fMRI activation maps across language areas during auditory and reading tasks to determine lateralization. Possible scores for LI range from −1 (strongly left-hemisphere dominant) to 1 (strongly right-hemisphere dominant). Concordance between fMRI and Wada was estimated using Cohen's Kappa coefficient. Association between the LI scores from the auditory and reading tasks was tested using Spearman's rank correlation coefficient. Results: The fMRI-based laterality indices were concordant with results from Wada testing in 91.4% of patients during the reading task (κ =.55) and 96.9% of patients during the auditory task (κ =.79). The mean LIs for the reading and auditory tasks were −0.52 ± 0.43 and −0.68 ± 0.42, respectively. The LI scores for the language and reading tasks were strongly correlated, r(30) = 0.57 (p = 0.001). Conclusion: Our findings suggest that fMRI is generally an accurate, low-risk alternative to Wada testing for language lateralization. However, when fMRI indicates atypical language lateralization (e.g., bilateral dominance), patients may benefit from subsequent Wada testing or intraoperative language mapping. [ABSTRACT FROM AUTHOR]

Background: In temporal lobe epilepsy (TLE), estimating the potential risk of language dysfunction before surgery is a necessary procedure. Functional MRI (fMRI) is considered the most useful to determine language lateralization noninvasively. However, there are no standardized language fMRI protocols, and several issues remain unresolved. In particular, the language tasks normally used are predominantly active paradigms that require the overt participation of patients, making assessment difficult for pediatric patients or patients with intellectual disabilities. In this study, task-based fMRI with passive narrative listening was applied to evaluate speech comprehension to estimate language function in Japanese-speaking patients with drug-resistant TLE. Methods: Twenty-one patients (six with intellectual disabilities) participated. Patients listened to passive auditory stimuli with combinations of forward and silent playback, and forward and backward playback. The activation results were extracted using a block design, and lateralization indices were calculated. The obtained fMRI results were compared to the results of the Wada test. Results: The concordance rate between fMRI and the Wada test was 95.2%. Meaningful responses were successfully obtained even from participants with intellectual disabilities. Conclusions: This passive fMRI paradigm can provide safe and easy presurgical language evaluation, particularly for individuals who may not readily engage in active paradigms.

The Wada test is the gold standard for determining language-dominant hemisphere. However, the precise determination of language areas in each patient requires more invasive methods, such as electrocortical stimulation. Some studies have reported the use of anesthetic injection into selective cerebral arteries to predict postoperative function. To assess the function of the anterior and posterior language areas separately, we developed an advanced test named the “super-selective Wada test” (ssWada). The ssWada procedure is as follows: an endovascular neurosurgeon identifies the arterial branches of the middle cerebral artery (MCA) perfusing the anterior language area of the inferior frontal gyrus and the posterior language area of the posterior part of the superior temporal gyrus using angiography. Behavioral neurologists assess language symptoms before and after propofol administration using a microcatheter tip in the selected arterial branch. From 30 serial patients with epilepsy who underwent ssWada test at Tohoku University Hospital, we retrospectively reviewed patients in whom multiple areas in the bilateral MCA region was examined. Eight cases were identified in this study. All eight cases had been considered for resection of the area overlapping the classical language area. Three of the eight cases were left-dominant, and the within-hemisphere distribution was also considered typical. One case was determined to be left-dominant but atypical in the intra-hemispheric functional distribution. Two cases were right-dominant, and the intra-hemispheric functional distribution was considered a mirror image of the typical pattern. The remaining two cases were considered atypical, not only in terms of bilateral language function, but also in terms of anterior-posterior functional distribution. This case series demonstrates the potential utility of ssWada in revealing separate function of the anterior and posterior language areas. The ssWada allows simulation of local surgical brain resection and detailed investigation of language function, which potentially contributes to planning the resection area. Although indications for ssWada are quite limited, it could play a complementary role to noninvasive testing because it provides information related to resection using a different approach.

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Wada test is an invasive procedure used in the preoperative evaluation for epilepsy surgery to determine language lateralization, postoperative risk of amnesia syndrome, and to assess the risk of memory deficits. It involves injection of amobarbital into internal carotid artery of the affected hemisphere followed by the healthy hemisphere to shut down brain function. We performed an observational study evaluating the density spectral array (DSA) of the bilateral bispectral index VISTA™ Monitoring System (BVMS) in 6 patients with drug-resistant epilepsy undergoing Wada test. DSA revealed the presence of bifrontal alpha waves in absence of loss of consciousness in all patients.

In high-stake cases (e.g., evaluating surgical candidacy for epilepsy) where neuropsychological evaluation is essential to care, it is important to have culturally and linguistically appropriate and accessible neuropsychological instruments and procedures for use with deaf individuals who use American Sign Language (ASL). Faced with these ethical and professional issues, clinicians may be unable to provide equitable services without consulting with other psychologists and collaborating with the patient and interpreter. This is a case report describing a 43-year-old male with bilateral sensorineural deafness and a lifelong history of drug-resistant temporal lobe epilepsy who presented as a candidate for a comprehensive neurological workup to determine surgical candidacy. He was bilingual (ASL and written English). We describe all aspects of the evaluation, including functional magnetic resonance imaging (fMRI) and Wada testing, using an ASL interpreter. Results from the neuropsychological evaluation were not clearly lateralizing, but suggested greater compromise to the non-dominant right hemisphere. fMRI and Wada test results revealed language and verbal memory functions were lateralized to the left hemisphere. The patient was deemed to be an adequate candidate for surgical resection of portions of the right hemisphere. Comprehensive assessment of neuropsychological functioning in deaf persons who use ASL is feasible. This case report illustrates the important considerations relevant to neuropsychologists providing culturally and linguistically informed assessments to deaf ASL users with epilepsy. Additional research in this area will support future efforts to develop effective and efficient models that could be implemented across different settings. Moreover, clinical guidance is warranted to guide professionals interested in promoting access to high quality neuropsychological services.

Background: Anti‐seizure medications (ASMs) have been related to poor cognitive function, but their relationship with intracarotid amobarbital procedure (IAP) results remains unclear. Aims of the Study: To elucidate whether the number and drug load of ASMs are associated with memory scores of the IAP and the neuropsychological assessment. Methods: Fifty‐nine adult patients with drug‐resistant epilepsy (mean age = 36.1, SD = 11.6) underwent bilateral IAP (with drawings and words as memory items) and a neuropsychological assessment to assess the risk of post‐surgical memory decline. Total ASM drug load was calculated by summing the daily dose/defined daily dose ratio of every ASM of each patient. Pearson's correlations and hierarchical regressions were computed. Results: Total IAP memory score was associated with total ASM drug load (r = −0.30, p = 0.02) and seizure frequency (r = −0.25, p = 0.05). After controlling clinical variables, total ASM drug load explained 16% of the variance of total IAP memory score. This relationship was especially prominent in patients with left hemisphere focus (r = −0.33, p = 0.04). The number of current ASMs was not related to IAP memory score (r = −0.16, p = 0.24). The number or drug load of ASMs were not related to neuropsychological assessment results (for all, p > 0.07). Conclusions: Our findings suggest that total drug load can be a confounding variable in the IAP memory performance that could explain, at least in part, the reverse asymmetries reported in different studies. [ABSTRACT FROM AUTHOR]

Objective: In epilepsy surgery, which aims to treat seizures and thereby to improve the lives of persons with drug‐resistant epilepsy, the chances of attaining seizure relief must be carefully weighed against the risks of complications and expected adverse events. The interpretation of data regarding complications of epilepsy surgery and invasive diagnostic procedures is hampered by a lack of uniform definitions and method of data collection. Methods: Based on a review of previous definitions and classifications of complications, we developed a proposal for a new classification. This proposal was then subject to revisions after expert opinion within E‐pilepsy, an EU‐funded European pilot network of reference centers in refractory epilepsy and epilepsy surgery, later incorporated into the ERN (European Reference Network) EpiCARE. This version was discussed with recognized experts, and a final protocol was agreed to after further revision. The final protocol was evaluated in practical use over 1 year in three of the participating centers. One hundred seventy‐four consecutive procedures were included with 35 reported complications. Results: This report presents a multidimensional classification of complications in epilepsy surgery and invasive diagnostic procedures, where complications are characterized in terms of their immediate effects, resulting permanent symptoms, and consequences on activities of daily living. Significance: We propose that the protocol will be helpful in the work to promote safety in epilepsy surgery and for future studies designed to identify risk factors for complications. Further work is needed to address the reporting of outcomes as regards neuropsychological function, activities of daily living, and quality of life. [ABSTRACT FROM AUTHOR]

ObjectiveFrom April 4 to August 1, 2014, Epilepsia conducted an online survey seeking opinions related to the use of the Wada test and intracranial electrodes in localizing cortical functions for epilepsy surgery patients. This study reports the findings of that poll.MethodsThe survey consisted of six questions. Two questions addressed: (1) If a Wada test was always necessary for patients with temporal lobe epilepsy; and (2) if magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) data could replace intracranial electrodes in localizing cortical motor-sensory and language functions. Four questions addressed the type of medical personnel, geographic region of residence based on International League Against Epilepsy (ILAE) regions, if responders had read the paper, and if they were ILAE/International Bureau for Epilepsy (IBE) members.ResultsOf 115 that started the survey, 92 (80%) completed it, and most were epilepsy specialists (87%) from North America (49%) and Europe (28%). Of responders, 85% indicated that Wada tests were unnecessary for temporal lobe epilepsy surgery patients. There were differences based on residency, with 100% of those from Europe indicating that the Wada test was unnecessary compared with 75% of those from North America (p = 0.01). Of responders, 56% indicated that intracranial electrodes were necessary to localize functional cortex.SignificanceThis survey found that the majority considered the Wada test unnecessary for temporal lobe epilepsy surgery patients, with more of those from Europe saying it is not needed compared with North America. In addition, just over half indicated that intracranial electrodes are still needed to localize motor-sensory and language functions. These findings, although based on opinions, support that there are divergent views on the use of these procedures in epilepsy surgery patients that require additional study.

In recent years, the clinical usefulness of the Wada test (WT) has been debated among researchers in the field. Therefore, we aimed to assess its contribution to the prediction of change in verbal learning and verbal memory function after epilepsy surgery. Data from 56 patients with temporal lobe epilepsy who underwent WT and subsequent surgery were analyzed retrospectively. Additionally, a standard neuropsychological assessment evaluating attentional, learning and memory, visuospatial, language, and executive function was performed both before and 12 months after surgery. Hierarchical linear regression analyses were used to determine the incremental value of WT results over socio-demographic, clinical, and neuropsychological characteristics in predicting postsurgical change in patients' verbal learning and verbal memory function. The incorporation of WT results significantly improved the prediction models of postsurgical change in verbal learning (∆R2 = 0.233, p =.032) and verbal memory function (∆R2 = 0.386, p =.005). Presurgical performance and WT scores accounted for 41.8% of the variance in postsurgical change in verbal learning function, and 51.1% of the variance in postsurgical change in verbal memory function. Our findings confirm that WT results are of significant incremental value for the prediction of postsurgical change in verbal learning and verbal memory function. Thus, the WT contributes to determining the risks of epilepsy surgery and, therefore, remains an important part of the presurgical work-up of selected patients with clear clinical indications. [ABSTRACT FROM AUTHOR]

Background: In the Wada test, one hemisphere is selectively anaesthetised by unilateral intracarotid injection of a fast-acting anaesthetic agent. This gives a unique opportunity to observe the functions and physiological activity of one hemisphere while anaesthetising the other, allowing direct comparisons between brain states and hemispheres that are not possible in any other setting. Aim: To test whether potential measures of consciousness would be affected by selective anaesthesia of one hemisphere, and reliably distinguish the states of the anesthetised and non-anesthetised hemispheres. Methods: We analysed EEG data from 7 patients undergoing Wada-tests in preparation for neurosurgery and computed several measures reported to correlate with the state of consciousness: power spectral density, functional connectivity, and measures of signal diversity. These measures were compared between conditions (normal rest vs. unilateral anaesthesia) and hemispheres (injected vs. non-injected), and used with a support vector machine to classify the state and site of injection objectively from individual patient's recordings. Results: Although brain function, assessed behaviourally, appeared to be substantially altered only on the injected side, we found large bilateral changes in power spectral density for all frequency bands tested, and functional connectivity changed significantly both between and within both hemispheres. Surprisingly, we found no statistically significant differences in the measures of signal diversity between hemispheres or states, for the group of 7 patients, although 4 of the individual patients showed a significant decrease in signal diversity on the injected side. Nevertheless, including signal diversity measures improved the classification results, indicating that these measures carry at least some non-redundant information about the condition and injection site. We propose that several of these results may be explained by conduction of activity, via the corpus callosum, from the injected to the contralateral hemisphere and vice versa, without substantially affecting the function of the receiving hemisphere, thus reflecting what we call “cross-state unreceptiveness”.

In the past, the eloquent areas could be deliberately localised by the invasive Wada test. The very rare cases of dissociated crossed speech areas were accidentally found based on the clinical symptomatology. Today functional magnetic resonance imaging (fMRI)-based imaging can be employed to non-invasively localise the eloquent areas in brain tumour patients for therapy planning. A 41-year-old, left-handed man with a low-grade glioma in the left frontal operculum extending to the insular cortex, tension headaches, and anomic aphasia over 5 months underwent a pre-operative speech area localisation fMRI measurement, which revealed the evidence of the transhemispheric disposition, where the dominant Wernicke speech area is located on the left and the Broca’s area is strongly lateralised to the right hemisphere. The outcome of the Wada test and the intraoperative cortico-subcortical stimulation mapping were congruent with this finding. After tumour removal, language area function was fully preserved. Upon the occurrence of brain tumours with a risk of impaired speech function, the rare dissociate crossed speech areas disposition may gain a clinically relevant meaning by allowing for more extended tumour removal. Hence, for its identification, diagnostics which take into account both brain hemispheres, such as fMRI, are recommended.

Objective: The intracarotid amobarbital procedure (IAP) is the current “gold standard” in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG). Methods: We recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and—from the vector sum of signals of this gradiometer pair—calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L–R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres. Results: The laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003). Significance: This simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples. [ABSTRACT FROM AUTHOR]

Objective The intracarotid sodium amytal procedure (the “Wada test”) has for many years been the gold standard for language and memory lateralization and remains an important part of presurgical analysis for patients with medically intractable seizures. Due to shortages in the key sedative (amobarbital), neuropsychologists have turned to alternatives such as propofol. Our aim was to investigate the safety and efficacy of propofol relative to amobarbital in the Wada test. Methods We performed a retrospective review of the 97 Wada procedures performed at University of Iowa Hospitals and Clinics from 2007 through mid-2015. Results Propofol produced similar lateralization rates as amobarbital for both language and memory. Similar rates of patients in each group went on to have the resection surgery. With regard to safety, there were no differences found in average rate or severity of adverse effects. None of the demographic characteristics reviewed were predictive of increased risk for either drug. Significance These findings support previous studies indicating that propofol is as safe and efficacious as amobarbital, and can continue to be used in Wada procedures with confidence. [ABSTRACT FROM AUTHOR]

The Wada test remains the traditional test for lateralizing language and memory function prior to epilepsy surgery. Functional imaging, particularly functional MRI (fMRI), has made progress in the language domain, but less so in the memory domain. Magnetoencephalography (MEG) has received less research attention, but shows promise, particularly for language lateralization. We recruited a consecutive sample of 19 patients with epilepsy who had completed presurgical work-up, including the Wada test, and compared fMRI (memory) and MEG (language and memory) with Wada test results. The main research question was the concordance between Wada and these two imaging techniques as preepilepsy surgery investigations. We were also interested in the acceptability of the three techniques to patients. Concordance rates (N = 16) were nonsignificant (Cohen's Kappa) between fMRI and Wada test (memory) and between MEG and Wada test (memory and language). The Wada test was a well-established protocol used at several epilepsy surgery centers in the UK. Patients generally found the Wada test an odd, but not aversive procedure. Sixteen (84%) patients who were scanned reported some level of obtundation in MEG. We present these discordant findings in support of the position that functional imaging and the Wada test are distinctive procedures, with little in the way of overlapping mechanisms, and that patient's experience should be taken into account when procedures are selected and offered to them. [ABSTRACT FROM AUTHOR]

From 1st January 2017 higenamine was added on the WADA (World Anti-doping Agency) Prohibited list under S3 group beta-2 agonists as at all times banned substance for the athletes. The main origine of higenamine (or norcoclaurine) are different plants including Nandina domestica , Aconitum carmichaelii , Asarum heterotropioides , Galium divaricatum , Annona squamosa , Nelumbo nucifera etc. Higenamine main use is related to weight loss and it could be found (un)labeled in different dietary supplements. The objective of this study was development of sensitive and reliable UHPLC/MS/MS method for determination of higenamine in various dietary supplement samples. In order to obtain high method sensitivity, hydrophilic interaction liquid chromatography (HILIC) mode was applied. Separation was carried out on UHPLC Acquity BEH HILIC analytical column (2.1 mm × 100 mm, 1.7 μm particle size). Mobile phase consisted of 0.1% formic acid in water and acetonitrile, respectively, was mixed in ratio of 30:70, v/v. Flow rate was set at 0.2 mL min −1 . Quercetin was used as an internal standard. ESI (+) source ionization mode using multi reaction monitoring (MRM) mode was utilized and three ion transitions of higenamine were followed 272.08 → 107.01, 272.08 → 161.07 and 272.08 → 77.08. Developed method was fully validated and applied for identification and quantification of higenamine in different dietary supplements. According to the results, the most of investigated supplements were free of higenamine, and on the other hand, presence of higenamine was confirmed in some samples while it was not declared on the label. [ABSTRACT FROM AUTHOR]

Purpose A previous study showed that assessment of language laterality could be improved by adding grammar tests to the recovery phase of the intracarotid amobarbital procedure (IAP) (Połczyńska et al. 2014). The aim of this study was to further investigate the extent to which grammar tests lateralize language function during the recovery phase of the IAP in a larger patient sample. Methods Forty patients with drug-resistant epilepsy (14 females, thirty-two right-handed, mean age 38.5 years, SD = 10.6) participated in this study. On EEG, 24 patients had seizures originating in the left hemisphere (LH), 13 in the right hemisphere (RH), and 4 demonstrated mixed seizure origin. Thirty participants (75%) had bilateral injections, and ten (25%) had unilateral injections (five RH and five LH). Based on results from the encoding phase, we segregated our study participants to a LH language dominant and a mixed dominance group. In the recovery phase of the IAP, the participants were administered a new grammar test (the CYCLE-N) and a standard language test. We analyzed the laterality index measure and effect sizes in the two tests. Key findings In the LH-dominant group, the CYCLE-N generated more profound language deficits in the recovery phase than the standard after injection to either hemisphere (p < 0.001). At the same time, the laterality index for the grammar tasks was still higher than for the standard tests. Critically, the CYCLE-N administered in the recovery phase was nearly as effective as the standard tests given during the encoding phase. Significance The results may be significant for individuals with epilepsy undergoing IAP. The grammar tests may be a highly efficient measure for lateralizing language function in the recovery phase. [ABSTRACT FROM AUTHOR]

Introduction Cerebral hemispherotomy is a surgical method with a high rate of seizure reduction in patients with intractable epilepsy. However, there is a probability of postoperative motor deficits. The objective of this study was to investigate whether the Wada test can help predict motor function outcomes after hemispherotomy and, therefore, may be useful in decision-making and patient selection. Patients and method A total of 13 patients with hemispherical intractable epilepsy underwent hemispherical disconnection surgeries. Six of them underwent the Wada test to evaluate motor function and language function followed by peri-insula hemispherotomy. The patients’ age ranged from 11 to 45 years (mean 27 years). Results Three of six patients had reduced dexterity on the Wada test. The finger motor function in the other patients did not change on the Wada test. Postoperatively, all patients who had decreased fine motor movement on the Wada test showed postoperative clumsiness of their hands and fingers. Conclusions The Wada test might predict postoperative fine finger motor deficit after hemispherotomy. This study showed that gross motor function was compensated in the ipsilateral hemisphere, whereas fine finger motor movement function remained in the contralateral frontal cortex. [ABSTRACT FROM AUTHOR]

In the past, the eloquent areas could be deliberately localised by the invasive Wada test. The very rare cases of dissociated crossed speech areas were accidentally found based on the clinical symptomatology. Today functional magnetic resonance imaging (fMRI)-based imaging can be employed to non-invasively localise the eloquent areas in brain tumour patients for therapy planning. A 41-year-old, left-handed man with a low-grade glioma in the left frontal operculum extending to the insular cortex, tension headaches, and anomic aphasia over 5 months underwent a pre-operative speech area localisation fMRI measurement, which revealed the evidence of the transhemispheric disposition, where the dominant Wernicke speech area is located on the left and the Broca's area is strongly lateralised to the right hemisphere. The outcome of the Wada test and the intraoperative cortico-subcortical stimulation mapping were congruent with this finding. After tumour removal, language area function was fully preserved. Upon the occurrence of brain tumours with a risk of impaired speech function, the rare dissociate crossed speech areas disposition may gain a clinically relevant meaning by allowing for more extended tumour removal. Hence, for its identification, diagnostics which take into account both brain hemispheres, such as fMRI, are recommended. [ABSTRACT FROM AUTHOR]

Surgical management of epilepsy is an established safe and effective way in improving patients' seizure frequency and overall morbidity. A robust array of options is available to carry out an in-depth evaluation of a surgical candidate in epilepsy. However, underutilisation of the available options may seriously challange post-operative outcomes. In this paper, we discuss the different aspects of various non-invasive and invasive procedures available to evaluate a surgical candidate of epilepsy and discuss their relative advantages and position in the diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the concordance of language lateralization between functional magnetic resonance imaging (fMRI) using Thai version of language paradigm and Wada test or awake surgery with direct cortical brain stimulation (DCS). Material and Method: Retrospective study of thirteen patients (3 males and 10 females with mean age of 33.9 years old) with epilepsy (7 cases) or brain tumor (6 cases) was performed. Every patient underwent both fMRI (word generation, verb generation, naming picture, and sentence completion tasks) and Wada test or awake surgery with DCS (defined as the gold standard). The lateralization index (LI) of fMRI was automatically calculated by using the LI-toolbox on SPM8. The hemispheric lateralization was also evaluated visually. The concordance between fMRI and gold standard were analyzed. Results: The concordance between the lateralization of fMRI by visual assessment and gold standard was 92.3%. Concordance between the calculated LI by fMRI and gold standard was varied along with the task and regional calculation method. The concordance was good in all tasks (except for naming picture task) when using calculated LI from frontal or whole brain excluded cerebellum and occipital lobe (range 76.92 to 88.98% and 76.92 to 92.31%, respectively). Conclusion: There was good concordance between fMRI and gold standard. Regional calculation from frontal lobes and whole brain excluded cerebellum and occipital lobes gave the best results. The results supported feasibility to use the fMRI with Thai language paradigm as an alternative way to determine the language dominant hemisphere in Thai patients. In case of language dominant hemisphere is unclear, further invasive investigation of language mapping such as Wada test or DCS is crucial. [ABSTRACT FROM AUTHOR]

Background: Epilepsy surgery offers an effective treatment to achieve seizure freedom in refractory temporal lobe epilepsy. Since left temporal lobe surgery can be associated with verbal memory deterioration, control of cognitive decline is a main goal of therapy. This study analyzes the prognostic value of intracarotid amobarbital procedure (Wada test) in addition to specific neuropsychological and clinical variables for postoperative memory changes., Method: Between 2013 and 2021 thirty-six patients (18 females, 18 males, mean age 41.0 years) from the Epilepsy Center Erlangen (ECE) with left hemispheric temporal lobe epilepsy underwent neuropsychological assessment preoperatively - including the Wada test - and six months postoperatively. In addition, a group of 92 patients (40 females, 52 males, mean age 36.1 years) with left or right hemispheric focus who underwent Wada test and surgery before 2013 was included as a standardization group. In all patients Wada test was carried out preoperatively to determine language dominance and memory capacity., Results: Postoperative verbal memory scores showed no significant difference from preoperative performance. Preoperative verbal memory performance as well as the hippocampal resection extent is particularly important in predicting postoperative verbal memory change. After left temporal lobe surgery, a significantly higher postoperative functional level was shown for figural memory. Specifically, a good contralateral hemispheric performance level assessed by the Wada test proved to be a compensatory factor for postoperative losses., Conclusion: The Wada test is no longer necessary as a diagnostic tool for a broad group of patients with temporal lobe epilepsy. However, it can be useful for a subgroup of patients with clinical indicators such as nonspecific or incongruent preoperative verbal and figural memory impairments. In this study, Wada test data about the functional level of the contralateral hemisphere specifically allowed estimation of postoperative figural memory changes., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Wada test is commonly used to evaluate language and memory lateralization in candidates for epilepsy surgery. The spatial Brain Symmetry Index (BSI) quantifies inter-hemispheric differences in the EEG. Its application has been shown to be feasible during Wada testing. We developed a method for the quantification of EEG asymmetry that matches visual assessments of the EEG better than BSI. Fifty-three patients' EEG data, with a total of 85 injections were analyzed. In a step-wise, data-driven manner, multiple electrode and frequency band combinations were evaluated. Eventually, BSI, calculated using only the frontal electrodes F 3 and F 4 , was combined with a temporal measure of delta power in the central electrodes, C 3 and C 4 , into a new measure: cBSI. Using the area under the ROC curve (AUC), we showed that cBSI performs significantly better relative to BSI (median AUC 0.98 versus 0.96, p = 0.0015, Wilcoxon signed rank test). Our results showed that asymmetry detection was significantly improved by combining temporal with spatial qEEG measures. In the future, our combined qEEG measure could allow for a more objective way of monitoring EEG asymmetry, thereby increasing the feasibility of using EEG as a monitoring tool during the Wada test. Future studies should, however, validate our cBSI method in real time in the operating room or radiology suite. [ABSTRACT FROM AUTHOR]

Purpose The Wada test has been the gold standard for determining hemispheric language dominance (HLD) in the presurgical evaluation of patients scheduled for neurosurgical procedures. As it poses inherent risks associated with intra-arterial catheter techniques and as it occasionally fails to indicate language dominance, an alternative reliable test is needed. We quantitatively assessed the results of functional magnetic resonance imaging (fMRI) using the Shiritori task, a Japanese word chain, to identify the threshold for correctly predicting HLD. Methods The subjects were 28 patients with intractable epilepsy scheduled to undergo the Wada test and focus resection. We set the region of interest (ROI) on the bilateral Brodmann areas 44 and 45 (BA 44 and 45). To compare the functional activity at both ROIs we calculated the language laterality index (LI) using the formula: [VL − VR]/[VL + VR] × 100, where VL and VR indicated the number of activated voxels in the left and right ROIs, respectively. Results As 2 patients were excluded due to the lack of activation in either ROI, the final study population consisted of 26 patients. By the Wada test, HLD was left in 20, right in 3, and equivocal in 3. At a cut-off of LI + 50, the predictive sensitivity and specificity for left HLD were 85% (17/20) and 100%; right HLD was predicted in a single patient (sensitivity 33.3%, specificity 100%). Conclusion The fMRI using the Shiritori task showed good activation in ROI of BA 44 and 45. At a cut-off of LI + 50, LI of BA 44 and 45 predicted HLD identified by the Wada test with high specificity. [ABSTRACT FROM AUTHOR]

The Wada test is widely used in the presurgical evaluation of potential temporal lobectomy patients to predict postoperative memory function. Expected asymmetry (EA), defined as Wada memory lateralized to the nonsurgical hemisphere, or a higher score after injection of the surgical hemisphere would be considered favorable in terms of postoperative memory outcome. However, in some cases, nonlateralized memory (NM) results, with no appreciable asymmetry, may occur because of impaired scores after both injections, often leading to denial of surgery. The reason for such nonlateralized Wada memory in patients with intractable temporal lobe epilepsy (TLE) remains unclear. Given that quantitative morphometric magnetic resonance imaging studies in TLE patients have shown bilateral regional atrophy in temporal and extratemporal structures, we hypothesized that the volume loss in contralateral temporal structures could contribute to nonlateralized Wada memory performance. To investigate this, we examined the relationship between the volume changes of temporal structures and Wada memory scores in patients with intractable TLE with mesial temporal sclerosis (MTS) using an age- and gender-matched control group. Memory was considered nonlateralized if the absolute difference in the total correct recall scores between ipsilateral and contralateral injections was <11%. Among 21 patients, Wada memory was lateralized in 15 and nonlateralized in 6 patients, with all the nonlateralized scores being observed in left TLE. The recall scores after ipsilateral injection were significantly lower in patients with an NM profile than an EA profile (23 ± 14% vs. 59 ± 18% correct recall, p ≤ 0.001). However, the recall scores after contralateral injection were low but similar between the two groups (25 ± 17% vs. 25 ± 15% correct recall, p = 0.97). Compared to controls, all the patients showed greater volume loss in the temporal regions. However, patients with a NM profile showed significantly more volume loss than those with a lateralized memory profile in both contralateral and ipsilateral temporal regions ( p < 0.05). Left hemispheric Wada memory performance correlated positively with the size of the left mesial and neocortical temporal structures ( r = 0.49–0.63, p = 0.005–0.04). Our study suggests that volume loss in the nonsurgical temporal structures is associated with nonlateralized Wada memory results in patients with intractable TLE. [ABSTRACT FROM AUTHOR]

I argue that if minds supervene on the intrinsic physical properties of things like brains, then typical human brains host many minds at once. Support comes from science-nonfiction realities that, unlike split-brain cases, have received little direct attention from philosophers. One of these realities is that some patients are functioning (albeit impaired) and phenomenally conscious by all medical and commonsense accounts despite the fact that they have undergone a hemispherectomy: an entire brain hemisphere has been fully detached. Another is the Wada test, in which a patient has each hemisphere anesthetized, one after the other, while the other hemisphere is awake and functioning--again, phenomenally conscious by any standard. I will argue that hemispherectomies, Wada tests, and related procedures each present cases in which the minds that exist after the detachment (or anesthetization) of a hemisphere are surviving minds which must be associated with the surviving (or un-anesthetized) hemisphere. I will argue that such surviving minds existed before the medical procedure, instantiated by the then-intact hemisphere that was due to survive the loss of its complementary hemisphere. If so, then the typical subject has at least three minds: a "left hemisphere mind", a "right hemisphere mind", and a "whole brain mind". But the argument generalizes to cases in which smaller portions of the brain are lost, yielding a great number of additional minds, some overlapping. Some important ethical implications are raised and briefly examined. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the effect of contralateral electrographic involvement on memory performance (measured by neuropsychological and Wada memory testing) in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS). Methods We studied 51 patients with medically-refractory epilepsy associated with unilateral MTS (27 women, 30/51, left MTS) submitted to prolonged non-invasive video-EEG monitoring and bilateral Wada testing. According to ictal electrographic involvement, patients were classified as: Contralateral ictal involvement, when one or more seizures evolved with rhythmic activity in the temporal region contralateral to the MTS or exclusive ipsilateral ictal involvement if all seizures showed ictal EEG activity exclusively on the MTS side. Wada testing involved a twelve-item memory paradigm. Wada memory asymmetry score was calculated for each patient subtracting the number of recalled items after injection on the lesion side from the number of recalled items after contralateral injection. Expected asymmetry (EA) was considered if Wada memory asymmetry > 0, and Symmetrical or Reversed memory asymmetry (S-RA) when ≤ 0. Neuropsychological testing was applied in the 51 patients and in 40 healthy controls. Verbal Memory was evaluated with the Rey Auditory Verbal Learning Test (RAVLT), considering the number of recalled items on immediate recall after the initial five consecutive encoding trials (RAVLT 6), a post-interference delayed (30 min) recall (RAVLT 7), and recall after 7 days. Nonverbal memory was tested with Wechsler Memory Scale-III (WMS-III) Faces subtests 1 e 2. Results Groups did not differ in demographic, clinical and video-EEG monitoring variables. S-RA was observed more frequently in the group with contralateral ictal involvement (57.2% vs. 27.0%; p: 0.03). Logistic regression analysis considering demographic, clinical, hippocampal volume and video-EEG monitoring variables showed contralateral ictal involvement as the only independent variable associated with S-RA (coefficient = 1.32, p = 0.029, odds ratio 3.77; 95% CI 1.1–12.47). Additionally, the patient group with contralateral ictal EEG involvement displayed worse verbal and nonverbal memory scores compared to healthy controls. Conclusion In this cohort of unilateral MTS patients, contralateral ictal involvement was associated with decreased memory performance on Wada and on neuropsychological testing. [ABSTRACT FROM AUTHOR]

This study aimed at establishing the predictive value of the markers CRP and IAP within 48 hours from admission in patients with acute pancreatitis and to compare their predictive value. In our study, we used CRP values at 48 hours after admission, as a predictive marker for the evolution to SAP and we compared them with IAP at 48 hours and with Ranson and APACHE II scores also calculated at 48 hours. We used ROC curves for representation and comparison of APACHE II score, Ranson score, CRP and IAP at 48 hours after admission and for determining their value as predictors of progression to severe acute pancreatitis. [ABSTRACT FROM AUTHOR]

The Wada test is an invasive procedure used to determine cerebral memory and language dominance as well as risk of cognitive deficits following neurosurgery. However, the potential risks of Wada testing have led some to consider foregoing Wada testing in candidates for resective epilepsy surgery with right hemispheric seizure onset. We present two atypical cases in which the Wada test showed unexpected memory and language lateralization. These cases underscore the importance of functional magnetic resonance in which imaging and Wada examination in right-handed individuals even when the lesion would not suggest atypical language representation. [ABSTRACT FROM AUTHOR]

The intracarotid sodium amytal test (ISAT or Wada Test) is a commonly performed procedure in the evaluation of patients with clinically refractory epilepsy candidates to epilepsy surgery. Its goal is to promote selective and temporary interruption of hemispheric functioning, seeking to define language lateralization and risk for memory compromise following surgery. Behavioral modification is expected during the procedure. Even though it may last several minutes, in most cases it is subtle and easily manageable. We report a series of patients in whom those reactions were unusually bizarre, including agitation and aggression. Apart of the obvious technical difficulties (patients required physical restraining) those behaviors potentially promote testing delay or abortion and more importantly, inaccurate data. We reviewed those cases, seeking for features that might have predicted their occurrence. Overall, reactions are rare, seen in less than 5% of the ISAT procedures. The barbiturate effect, patients' psychiatric profiles, hemisphere dominance or selectiveness of the injection were not validated as predictors. Thorough explanation, repetition and simulation may be of help in lessening the risk of those reactions.O teste do amital sódico intracarotídeo (TASI ou teste de Wada) é procedimento comum na avaliação de pacientes portadores de epilepsia clinicamente refratária candidatos a cirurgia de epilepsia. Tem por objetivo promover interrupção seletiva e temporária da função hemisferial, definindo lateralização de linguagem e risco de comprometimento de memória no pós-operatório. São esperadas mudanças comportamentais durante o teste, as quais podem durar vários minutos, porém, em geral, são sutis e facilmente manejáveis. Relatamos uma série de casos em que ocorreram comportamentos pouco usuais, bizarros, incluindo agitação e agressividade. Estes comportamentos comprometem o teste (paciente deve ser contido), podendo levar a atrasos ou mesmo abortamento do mesmo, além de produzir dados menos confiáveis. Os casos foram revisados, visando a definição de preditores de sua ocorrência. Estas reações são raras (5% dos casos). Efeito barbitúrico, perfil psiquiátrico, dominância cerebral e seletividade da injeção não puderam ser validados como preditores. Explicações detalhadas, repetição e simulações podem ser utéis na prevenção deste tipo de ocorrência.

The Wada Test (WT) is part of the presurgical evaluation for refractory epilepsy. The WT is not standardized and the protocols differ in important ways, including stimulus type of material presented for memory testing, timing of presentations and methods of assessment. The aim of this study was to contribute to establish parameters for a WT to Brazilian population investigating the performance of 100 normal subjects, without medication. Two parallel models were used based on Montreal Procedure adapted from Gail Risse's (MEG-MN,EUA) protocol. The proportions of correct responses of normal subjects submitted to two parallel WT models were investigated and the two models were compared. The results showed that the two models are similar but significant differences among the stimulus type were observed. The results suggest that the stimulus type may influence the results of the WT and should be considered when constructing models and comparing different protocols.

Concern about postoperative worsening of cognitive functions after temporal lobe epilepsy surgery is an important issue. In this article we review our data on neuropsychological outcome after radiofrequency (RF) ablation of amygdalohippocampal complex (AHC). On a group level we found initial improvement in intelligence domains and unchanged memory scores one year after the surgery. During longitudinal follow-up, we found improvement in both intellectual and memory domains. This improvement was most pronounced up to two years after surgery. On an individual level, no patient worsened in any intellectual domain and most patients improved in memory. We hypothesize that this favorable outcome may be a consequence of minimization of collateral damage and incomplete destruction of target structures. We also summarize our experience with psychiatric complications of the procedure. [ABSTRACT FROM AUTHOR]

• The RNS System allows recording hippocampal intracranial EEG during Wada testing. • Intracarotid methohexital induces marked ipsilateral hippocampal spiking. • Methohexital injections could also induce ipsilateral hippocampal seizures. • These findings might explain how Wada testing can disrupt medial temporal function without direct perfusion of anesthetic. Wada testing remains an important component of pre-surgical testing to assess the feasibility of temporal lobectomy for patients with intractable epilepsy. In this procedure, an anesthetic is injected into either internal carotid artery while memory and language testing is performed, simulating the effect of temporal lobe resection. The mechanism remains poorly understood because the hippocampal vasculature is predominantly via the posterior circulation. We recorded hippocampal EEG during bilateral methohexital Wada testing in three patients who had previously been implanted with a responsive neurostimulation system (RNS) to determine the effect of the injections on hippocampal activity. In all six injections from three patients, methohexital caused immediate, transient increases in hippocampal spikes. With at least two of these injections, the electrographic changes were consistent with electrographic seizures. In all cases, the epileptiform activity was not apparent on scalp EEG and was without obvious clinical correlate other than the negative findings expected from the anesthetic. The results demonstrate the utility of intracranial EEG during Wada testing and suggest that the elicitation of seizures or continuous spiking might contribute to dysfunction of the hippocampus during the Wada test. We hypothesize that this effect is due to disconnection and disinhibition of medial temporal structures. [ABSTRACT FROM AUTHOR]

This study aimed to define the number and type of complications associated with the Wada test at an academic medical center for comparison to previous reports. We performed a retrospective review of medical records for patients who underwent the Wada test at the University of Michigan between April 1991 and June 2013. Information was collected regarding the angiography procedure and the immediate postoperative period to assess for both clinical and angiographic complications. A total of 436 patients were identified who underwent the Wada procedure between April 1991 and June 2013, and 431 patients were included in the final analysis. Twenty-five patients (5.8%) had notable clinical events associated with the Wada test. Nine patients (2.1%) had clinical events meeting criteria for complication, which included seizures, status epilepticus, internal carotid artery vasospasm, inadvertent injection of anesthetic in the external carotid artery, and transient encephalopathy. No complications were associated with significant morbidity or mortality. This retrospective review of patients undergoing the Wada test found significantly fewer associated complications in comparison to previously published studies, with no patients experiencing long-term morbidity. The Wada test should be considered a safe diagnostic tool for lateralizing language and memory. [ABSTRACT FROM AUTHOR]

Purpose Functional transcranial Doppler sonography (fTCD) is a valid and non-invasive tool for determining language dominance, e.g. in the context of presurgical evaluations. Beyond this, fTCD might be an ideal tool to study dynamics in language dominance over time. However, an essential prerequisite would be a high test–retest reliability. This was addressed in the present study. Methods Test–retest reliability of hemispheric hemodynamics during open speech was determined in 11 male and 11 female healthy volunteers using the Animation Description Paradigm. Expressive language dominance was assessed weekly over an interval of 4–5 weeks. Results Internal consistency of the four measurements was excellent (split-half reliability 0.85–0.95), but test–retest reliability of the lateralization index was poor to moderate (rtt = 0.37–0.74). Controlling for gender, test–retest reliabilities were better in men (rtt = 0.67–0.78) as compared to women (rtt = 0.04–0.70). When arranging the assessments in women around day one of menstruation – all were on contraceptives – a significant shift from left hemisphere dominance toward bilaterality ( t = 2.2 p = 0.04) was evident around menstruation with significant reversal afterwards ( t = −3.4 p = 0.005). Conclusion A high intraindividual variability of language dominance patterns is indicated in women when assessed repeatedly by fTCD. Menstrual cycle appeared to be the source of inconsistency. The finding challenges the use of non-deactivating methods for language dominance assessment in epilepsy. Support for this is demonstrated with a female patient with epilepsy in whom language dominance assessed by repeated fMRI and fTCD varied concordantly with cycle but not so the repeated intracarotidal amobarbital test. [ABSTRACT FROM AUTHOR]

Objective The basal temporal language area (BTL) is known to be involved in the semantic processing of language. To investigate the neural connectivity between BTL and the posterior language area (PL), we used cortico-cortical evoked potential (CCEP) technique. Methods Four patients with intractable epilepsy who underwent presurgical evaluation with subdural electrodes were examined. All patients were right-handed and left language dominance by Wada test. We directly stimulated 20 pairs of electrodes placed on BTL in patient 1–3, putative BTL in patient 4, and PL in patient 1–4. In patient 4, all electrodes on the left temporal basal area were stimulated. Results We could record 132 CCEP responses including 40 responses by the left basal temporal stimulation in patient 4. The waveforms from PL to BTL were triphasic, while those from BTL to PL were biphasic. The mean latency of the first negative peak (N1) was shorter at BTL (31.8–41.0 ms; mean 35.1 ms) than at PL (39.6–73.2 ms; mean 52.3 ms). Conclusions We revealed the uneven bidirectional connection between BTL and PL. Significance We speculated that the two language areas are connected mainly through subcortical fibers from PL to BTL and through cortico-cortical fibers from BTL to PL, mediated by multisynaptic transmissions. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to compare the memory outcome following left anterior temporal lobectomy (ATL) between patients with a failed Wada test and patients who passed the Wada test. Methods From 1996 to 2002, we performed the Wada test on all patients with unilateral left mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and concordant electroclinical data before ATL. We used a 12-item recognition paradigm for memory testing and awarded a score of + 1 for each correct response and − 0.5 for each incorrect response. No patient was denied surgery on the basis of Wada scores. We assessed cognitive and memory functions using the Wechsler Adult Intelligence Scale and the Wechsler Memory Scale preoperatively and at one year after ATL. We compared the number of patients who showed decline in memory scores, as per the published reliable change indices, between the patients with a failed Wada test and the patients who passed the Wada test. Results Out of the 116 eligible patients with left MTLE-HS, 88 underwent bilateral Wada test, while 28 underwent ipsilateral Wada test. None of them developed postoperative amnesia. Approximately, one-third of patients with a failed Wada memory test when the failure was defined as a contralateral score of < 4, as an ipsilateral score of > 8, and as an asymmetry score of < 0. The patients with Wada memory failure had a longer pre-ATL duration of epilepsy (p < 0.003). The memory and quality-of-life outcomes did not differ between the group with a failed Wada memory test and the group who passed the Wada memory test. The results remained the same when analyses were repeated at various other cutoff points. Conclusion The patients with left MTLE-HS with concordant electroclinical, MRI, and neuropsychological data should not be denied ATL solely on the basis of Wada memory test results. [ABSTRACT FROM AUTHOR]

Summary The Wada test was adapted from the procedure described by Wada in 1964. It still has a role in the prognostic evaluation of memory disorders after mesial temporal lobectomy. The test consists of injecting a short-acting anesthetic into one hemisphere, under continuous EEG monitoring and during carotid catheterization, to verify the function of contralateral structures. Intracranial EEG recordings deliver signals with few artifacts, and which are quite specific of the zone explored. Three types of electrodes are in common use: (a) foramen ovale (FO) electrodes: electrodes can be inserted directly, without any stereotactic procedure, to provide easy and comparative EEG recordings of the lower and middle portions of the temporal lobe close to the hippocampus. These allow validation of the temporal lobe origin of seizures using FO electrodes recording coupled with scalp EEG; (b): subdural strip or grip electrodes. This relatively aggressive technique carries infectious and hemorrhagic risks and does not allow the exploration of deep cortical structures. However, it permits precise functional cortical mapping via electrical stimulation because of dense and regular positioning of electrodes over the cortical convexity; (c) stereotactically implanted depth electrodes (stereo-electroencephalography [SEEG]). Electrodes are individually planned and inserted within the brain parenchyma through small burr holes. This technique is less aggressive than subdural grid exploration. However it offers relatively limited spatial sampling that may be less well adapted to precise functional evaluation. It allows recording from deep cortical structures and can be argued to be the gold standard of presurgical EEG exploration. [ABSTRACT FROM AUTHOR]

Background Intracarotid amobarbital procedure (IAP) is acknowledged as the gold standard test for language lateralization. EEG is performed routinely during IAP to monitor the anesthetization of a brain hemisphere. Here, we studied the correlation between the early EEG changes using envelope trend and the clinical outcome of IAP. Method Fifty consecutive patients underwent IAP at Texas Children's Hospital (2004–2009). Intracarotid amobarbital procedure was considered “complete” or “incomplete” based on the outcome if the procedure was completed or aborted due to behavior changes. Envelope trend was used to calculate the median EEG amplitude changes within the first 60 s of IAP. Statistical analysis was performed to determine the role of EEG changes and clinical features on the procedure outcome. Results Only 30 IAP-EEG files were available for review. Amobarbital was administered at the dose of 60–150 mg (mean: 110 ± 20). The intracarotid amobarbital procedure was recorded as complete in 23 patients and incomplete in 7 patients. EEG changes occurred within the first few seconds following amobarbital injection. Following amobarbital injection, focal slowing was present in the ipsilateral frontal region or both ipsilateral and contralateral frontal regions. Elapsed time to the first EEG change or duration and change in median EEG amplitude in the ipsilateral frontal regions were indifferent between the complete and incomplete groups (p > 0.05). However, the median amplitude changes between the ipsilateral and contralateral frontal regions within each group were found significant only in the complete group (p < 0.05), suggesting ipsilateral without contralateral frontal slowing. Other than age at the time of IAP (p = 0.03), none of the other clinical features correlated with the clinical outcome of IAP (p > 0.05). Conclusion Early EEG changes during IAP using envelope trend may predict successful completion of the IAP test. Younger children are at risk of behavioral changes during IAP. [ABSTRACT FROM AUTHOR]

Summary Introduction Grammar is a core component of the language system, yet it is rarely assessed during the Wada (intracarotid amobarbital) test. It is hypothesized that adding grammar tests to the recovery phase of the Wada test will increase our ability to lateralize language function. Method Sixteen individuals (nine females, fifteen right-handed, mean age 38.4 years, SD = 10.7) with medically refractory temporal lobe epilepsy participated in the study. On EEG ten patients had seizures originating in the left hemisphere (LH), five in the right hemisphere (RH), and one was insufficiently lateralized. We included only patients who were LH-dominant on the standard test in the encoding phase of the Wada test. In the recovery phase of Wada testing the participants underwent evaluation with a standard language and a new test of grammar, the CYCLE-N. Ten patients underwent bilateral injections, six unilateral (one RH, five LH). Results As expected, injection in the LH decreased language performance to a greater extent than injection to the RH on both tests. However, the CYCLE-N produced more profound language deficits in the injected LH compared to the RH ( p = 0.01), whereas the standard tests did not cause such pronounced differences ( p = 0.2). Conclusion The results suggest that the standard tests did not significantly differentiate the effects of the injections and the CYCLE-N, for the most part, did. Our results are of particular relevance to patients who are too obtunded to speak in the encoding phase. In sum, the CYCLE-N may be helpful in assessing hemispheric dominance for language. [ABSTRACT FROM AUTHOR]

Summary In this study we validate passive language fMRI protocols designed for clinical application in pediatric epilepsy surgical planning as they do not require overt participation from patients. We introduced a set of quality checks that assess reliability of noninvasive fMRI mappings utilized for clinical purposes. We initially compared two fMRI language mapping paradigms, one active in nature (requiring participation from the patient) and the other passive in nature (requiring no participation from the patient). Group-level analysis in a healthy control cohort demonstrated similar activation of the putative language centers of the brain in the inferior frontal (IFG) and temporoparietal (TPG) regions. Additionally, we showed that passive language fMRI produced more left-lateralized activation in TPG (LI = +0.45) compared to the active task; with similarly robust left-lateralized IFG (LI = +0.24) activations using the passive task. We validated our recommended fMRI mapping protocols in a cohort of 15 pediatric epilepsy patients by direct comparison against the invasive clinical gold-standards. We found that language-specific TPG activation by fMRI agreed to within 9.2 mm to subdural localizations by invasive functional mapping in the same patients, and language dominance by fMRI agreed with Wada test results at 80% congruency in TPG and 73% congruency in IFG. Lastly, we tested the recommended passive language fMRI protocols in a cohort of very young patients and confirmed reliable language-specific activation patterns in that challenging cohort. We concluded that language activation maps can be reliably achieved using the passive language fMRI protocols we proposed even in very young (average 7.5 years old) or sedated pediatric epilepsy patients. [ABSTRACT FROM AUTHOR]

Speech and language-related functions tend to depend on the left hemisphere more than the right in most right-handed (dextral) participants. This relationship is less clear in non-right handed (adextral) people, resulting in surprisingly polarized opinion on whether or not they are as lateralized as right handers. The present analysis investigates this issue by largely ignoring methodological differences between the different neuroscientific approaches to language lateralization, as well as discrepancies in how dextral and adextral participants were recruited or defined. Here we evaluate the tendency for dextrals to be more left hemisphere dominant than adextrals, using random effects meta analyses. In spite of several limitations, including sample size (in the adextrals in particular), missing details on proportions of groups who show directional effects in many experiments, and so on the different paradigms all point to proportionally increased left hemispheric dominance in the dextrals. These results are analyzed in light of the theoretical importance of these subtle differences for understanding the cognitive neuroscience of language, as well as the unusual asymmetry in most adextrals. [ABSTRACT FROM AUTHOR]

Hemispheric language dominance and isolated hemispheric memory function evaluation can be undertaken with the intracarotid injection of a general anesthetic agent (Wada test). Amobarbital has been traditionally used as the anesthetic agent, but legal and commercial constraints limit its use. We evaluated the use of etomidate as an alternative agent for the Wada test in a series of 54 consecutive adult patients with mesial temporal sclerosis undergoing presurgical evaluation for epilepsy surgery. Language lateralization and hemispheric memory function evaluation were successfully achieved in all cases. Side effects (somnolence, tremor, and dystonia) were infrequent, minor, and transient and did not require interruption of the procedure. Etomidate appears to be a safe and effective alternative agent to amobarbital in the Wada test. Similarly to the amobarbital Wada test, the ability of the etomidate Wada test to predict postoperative memory decline remains unclear. [ABSTRACT FROM AUTHOR]

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task. Methods: Twenty-five patients with pharmaco-resistant epilepsy, including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects. Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and parietal language areas (Cohen's Kappa = 1, p < 0.001). fMRI agreed with Wada test in 12 out of 14 cases (85.7%) for Broca's area (Cohen's Kappa = 0.71, p = 0.024), while the agreement for temporal and temporo-parietal language areas were non-significant. Concordance between MEG and fMRI laterality indices was highest within the inferior frontal gyrus, with an agreement in 19/24 cases (79.2%), and non-significant for Wernicke's area. Spatial agreement between fMRI and MEG varied considerably between subjects and brain regions with the lowest Euclidean distances within the inferior frontal region of interest. Conclusion: Localizing the desynchronization of MEG beta power using a verb generation task is a promising tool for the identification of language dominance in the pre-surgical evaluation of epilepsy patients. The overall agreement between MEG and fMRI was lower than expected and might be attributed to differences within the baseline condition. A larger sample size and an adjustment of the experimental designs are needed to draw further conclusions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Herfurth, Harpaz, Roesch, Mueller, Walther, Kaltenhaeuser, Pauli, Goldstein, Hamer, Buchfelder, Doerfler, Prell and Rampp.)

Advances in functional imaging have provided noninvasive techniques to probe brain organization of multiple constructs including language and memory. Because of high overall rates of agreements with older techniques, including Wada testing and cortical stimulation mapping ( CSM), some have proposed that those approaches should be largely abandoned because of their invasiveness, and replaced with noninvasive functional imaging methods. High overall agreement, however, is based largely on concordant language lateralization in series dominated by cases of typical cerebral dominance. Advocating a universal switch from Wada testing and cortical stimulation mapping to functional magnetic resonance imaging (f MRI) or magnetoencephalography ( MEG) ignores the differences in specific expertise across epilepsy centers, many of which often have greater skill with one approach rather than the other, and that Wada, CSM, f MRI, and MEG protocols vary across institutions resulting in different outcomes and reliability. Specific patient characteristics also affect whether Wada or CSM might influence surgical management, making it difficult to accept broad recommendations against currently useful clinical tools. Although the development of noninvasive techniques has diminished the frequency of more invasive approaches, advocating their use to replace Wada testing and CSM across all epilepsy surgery programs without consideration of the different skills, protocols, and expertise at any given center site is ill-advised. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . [ABSTRACT FROM AUTHOR]